The number of mucosal disorders which are difficult to treat has considerably increased in recent times, and the increasing trend continues. The mucosal disorders which are difficult to treat nowadays include primarily candidoses of the oral and vaginal mucosa.
Candidoses are defined as infections usually caused by Candida albicans, but also by a large number of other Candida species which grow opportunistically (C. krusei, C. tropicalis, Candida glabrata and many others). The yeast-like fungi which are often present anyway in the oral cavity, the gastrointestinal tract and the vagina grow under particular conditions and assume parasitic/pathogenic characteristics. Yeast-like fungi are able in some circumstances to colonize the skin and its appendages, all mucosae near the skin and several internal organs (esophagus, lung etc.) and, in this event, induce a remarkably wide range of disorders.
The occurrence of a candidosis may be favored in particular by pregnancy, metabolic disorders, infectious diseases, tumors and immunodeficiencies. Locally favoring factors are regarded as being mechanical irritation (for example dentures), occlusion, moisture and moist heat.
The occurrence of extensive oral candidosis is nowadays regarded in most countries as one of the principal clinical signs of impaired functioning of the immune system. Persistent oral candidoses indicate in many HIV patients the transition to immunodecompensation. In advanced immunodeficiency there are also erosive, and sometimes ulcerative, inflammations involving the gingiva, and candidal balanitis, candidal vulvitis and Candida-related anal eczema are not uncommon. Intestinal infections and candidal sepsis are likewise observed.
In immunocompetent patients, nystatin is regarded as the agent of choice for local treatment of Candida infections, but clinical experience shows that nystatin therapy on its own is often insufficient in HIV-infected immunodeficient patients. In these cases, systemic therapy with antimycotics of the azole type is widely used. Candida strains resistant to azoles were virtually unknown up to 1989. However, the treatment of vaginal candidoses has often proven difficult due to the occurrence of mixed infections with the protozoal strains Trinchomonas vaginalis and Entamoeba histolytica. 
However, since the use of fluconazole for preventing recurrence of oropharyngeal candidoses in HIV patients, the number of azole resistances which have become known has increased dramatically. Up to and including the 1st half of 1995, 98 publications in the specialist literature reported resistance of Candida strains to azoles.
The documents EP 0 241 918 or U.S. Pat. No. 4,797,409 describe the preparation of 1-hydroxy-2-pyridones and their use for controlling mainly infections by fungi and yeast, and pharmaceuticals containing these compounds.
It is therefore an object of the present invention to provide topical pharmaceutical formulations which are suitable for breaking through exsistent intrinsic and acquired resistances of Candida strains to azoles, while simultaneously having activity on the problem organisms Trinchomonas vaginalis and Entamoeba histolytica. 
It has now been found that compounds of the formula I are outstandingly suitable for the treatment of candidoses caused by yeast strains with intrinsic and acquired azole resistance. Said compounds are also distinguished by their activity, which is sufficient for therapeutic purposes, on the problem organisms Trinchomonas vaginalis and Entamoeba histolytica which are often the cause of the development of mixed infections in cases of vaginal candidosis.
The invention relates to the use of the compound of the formula I 
in which R1, R2 and R3, which are identical or different, are hydrogen atom or alkyl with 1-4 carbon atoms, and R4 is a saturated hydrocarbon radical with 6 to 9 carbon atoms or a radical of the formula II 
where
X is S or O,
Y is a hydrogen atom or up to 2 halogen atoms such as chlorine and/or bromine,
Z is a single bond or the divalent radicals O, S, xe2x80x94CR2xe2x80x94(Rxe2x95x90H or C1-C4-alkyl) or other divalent radicals with 2-10 carbon and, where appropriate, oxygen and/or sulfur atoms linked to form a chain, andxe2x80x94when the radicals contain 2 or more oxygen and/or sulfur atomsxe2x80x94the latter must be separated from one another by at least 2 carbon atoms, and where 2 adjacent carbon atoms can also be linked together by a double bond, and the free valencies of the carbon atoms are saturated by H and/or C1-C4 alkyl groups,
Ar is an aromatic ring system which has up to two rings and can be substituted by up to three radicals from the group of fluorine, chlorine, bromine, methoxy, C1-C4-alkyl, trifluoromethyl and trifluoromethoxy,
for the preparation of a pharmaceutical for the treatment of fungal disorders caused by azole-resistant fungi.
The compounds according to the invention are furthermore suitable for the treatment of trichomoniasis, one of the commonest causes, which is spread around the world, of non-gonorrheal urethritis. The disorder is caused by the pathogen Trinchomonas vaginalis which is one of the protozoa.
The carbon chain members in the xe2x80x9cZxe2x80x9d radicals are preferably CH2 groups. If the CH2 groups are substituted by C1-C4-alkyl groups, CH3 and C2H5 are preferred substituents.
Examples of xe2x80x9cZxe2x80x9d radicals are:
xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94CH2xe2x80x94, xe2x80x94(CH2)mxe2x80x94(m=2-10), xe2x80x94C(CH3)2xe2x80x94, xe2x80x94CH2Oxe2x80x94, xe2x80x94OCH2xe2x80x94, xe2x80x94CH2Sxe2x80x94,
xe2x80x94S CH2xe2x80x94, xe2x80x94S CH (C2H5)xe2x80x94, xe2x80x94CHxe2x95x90CHxe2x80x94CH2Oxe2x80x94, xe2x80x94Oxe2x80x94CH2xe2x80x94CHxe2x95x90CHxe2x80x94CH2Oxe2x80x94, xe2x80x94O CH2xe2x80x94
CH2Oxe2x80x94, xe2x80x94O CH2xe2x80x94CH2CH2Oxe2x80x94, xe2x80x94S CH2 CH2 CH2 Sxe2x80x94, xe2x80x94S CH2 CH2 CH2 CH2 
xe2x80x94Oxe2x80x94, xe2x80x94S CH2 CH2 O CH2 CH2 Oxe2x80x94, xe2x80x94S CH2CH2 O CH2 CH2 Oxe2x80x94CH2 CH2 Sxe2x80x94, or xe2x80x94Sxe2x80x94CH2xe2x80x94C (CH3)2xe2x80x94CH2xe2x80x94Sxe2x80x94.
The radical xe2x80x9cSxe2x80x9d is a sulfur atom, and the radical xe2x80x9cOxe2x80x9d is an oxygen atom. The term xe2x80x9cArxe2x80x9d means phenyl and condensed systems such as naphthyl, tetrahydronaphthyl and indenyl, and isolated systems such as those derived from biphenyl, diphenylalkanes, diphenyl ethers and diphenyl thioethers.
Principal representatives of the class of compounds characterized by the formula I are:
6-[4-(4-chlorophenoxy)phenoxymethyl]-1-hydroxy4-methyl-2-pyridone;
6-[4-(2,4-dichlorophenoxy)phenoxymethyl]-1-hydroxy-4-methyl-2-pyridone;
6-(4-biphenylyloxymethyl)-1-hydroxy-4-methyl-2-pyridone;
6-(4-benzylphenoxymethyl)-1-hydroxy-4-methyl-2-pyridone;
6-[4-(2,4-dichlorobenzyloxy)phenoxymethyl]-1-hydroxy-4-methyl-2-pyridone;
6-[4-(4-chlorophenoxy)phenoxymethyl]-1-hydroxy-3,4-dimethyl-2-pyridone;
6-[4-(2,4-dichlorobenzyl)phenoxymethyl]-1-hydroxy-3,4-dimethyl-2-pyridone;
6-[4-(cinnamyloxy)phenoxymethyl]-1-hydroxy4-methyl-2-pyridone;
1-hydroxy-4-methyl-6-[4-(4-trifluoromethylphenoxy)phenoxymethyl]-2-pyridone;
1-hydroxy4-methyl-6-cyclohexyl-2-pyridone
or
1-hydroxy4-methyl-6-(2,4,4-trimethylpentyl)-2-pyridone.
The abovementioned compounds of the formula I can be employed both in free form and in the form of salts, and use in free form is preferred. The compounds of the formula I to be employed in the formulations can be prepared, for example, by processes disclosed in U.S. Pat. Nos. 2,540,218 or 4,797,409.
The term xe2x80x9cazole-resistant fungixe2x80x9d means all species of fungi or yeasts which have become resistant to antimycotics, for example to antimycotics which contain azole residues, such as fluconazole.
Immunosuppressed patients are preferably treated such as diabetics, asthmatics, smokers, AIDS patients, patients before and after transplants, cancer patients, patients chronically treated with antibiotics, cytostatics or corticosteroids, patients with antimycotic-resistant fungi, in particular patients with fluconazole-resistant fungi or elderly people.
Suitable for the use of said compounds according to the invention are liquid, semisolid and solid pharmaceutical formulations, in particular solutions, cream, ointment and gel formulations, and pastilles and pessaries.
The active substance is incorporated into the formulations according to the invention in amounts which are normally between about 0.05 and about 5%, preferably between 0.1 and 1%.
Topical treatment of candidoses caused by yeast strains with intrinsic and acquired azole resistance with the pharmaceuticals according to the invention is able to achieve an effective cure.
The compositions according to the invention can also be employed successfully for the treatment of vaginal candidoses with mixed infections by the protozoal strains Trinchomonas vaginalis and Entamoeba histolytica.